UNITED STATES PATENT AND TRADEMARK OFFICE
`
`BEFORE THE PATENT TRIAL AND APPEAL BOARD
`
`MYLAN PHARMACEUTICALS INC.,
`Petitioner,
`v.
`
`NOVO NORDISK A/S,
`Patent Owner.
`
`Case No. IPR2023-00724
`Patent No. 10,335,462
`
`DECLARATION OF WILLIAM J. JUSKO, PH.D., IN SUPPORT OF
`PETITION FOR INTER PARTES REVIEW OF
`U.S. PATENT NO. 10,335,462
`
`MPI EXHIBIT 1005 PAGE 1
`
`DR. REDDY’S LABORATORIES, INC.
`IPR2024-00009
`Ex. 1005, p. 1 of 132
`
`

`

`TABLE OF CONTENTS
`
`
`Page
`
`
`I.
`
`II.
`III.
`IV.
`V.
`
`QUALIFICATIONS AND BACKGROUND .......................................................... 9
`A.
`EDUCATION AND EXPERIENCE ..................................................................... 9
`B.
`PRIOR TESTIMONY ................................................................................... 13
`C.
`BASIS FOR OPINIONS AND MATERIALS CONSIDERED ...................................... 14
`D.
`RETENTION AND COMPENSATION ............................................................... 14
`LEGAL STANDARDS ...................................................................................... 14
`PERSON OF ORDINARY SKILL IN THE ART .................................................. 17
`BRIEF SUMMARY OF OPINIONS .................................................................... 18
`THE ’462 PATENT [EX. 1001] .......................................................................... 19
`A.
`THE SPECIFICATION AND CLAIMS OF THE ’462 PATENT .................................. 19
`B.
`THE PROSECUTION HISTORY OF THE ’462 PATENT ......................................... 21
`CLAIM CONSTRUCTION ................................................................................ 24
`VI.
`VII. BACKGROUND .............................................................................................. 26
`A.
`PHARMACOKINETICS AND PHARMACODYNAMICS .......................................... 26
`B.
`DRUG DEVELOPMENT - CLINICAL TRIAL DESIGN .......................................... 29
`C.
`PHARMACOKINETICS AND PHARMACODYNAMICS RELATED TO GLP-1 AND
`SEMAGLUTIDE ........................................................................................ 36
`1.
`GLP-1 ........................................................................................ 36
`2.
`GLP-1 derivatives ........................................................................ 37
`SEMAGLUTIDE CLINICAL TRIALS ................................................................ 45
`D.
`VIII. SCOPE AND CONTENT OF THE PRIOR ART ................................................... 49
`A. WO421 [EX. 1011] .................................................................................. 50
`B.
`LOVSHIN [EX. 1012] ................................................................................ 52
`C. WO537 [EX. 1015] .................................................................................. 54
`D.
`SEMAGLUTIDE CLINICAL TRIALS ................................................................ 56
`1.
`NCT657 [Ex. 1013] ...................................................................... 56
`2.
`NCT773 [Ex. 1014] ...................................................................... 58
`
`
`
`
`
`-2-
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`TABLE OF CONTENTS
`(continued)
`
`Page
`
`B.
`
`C.
`
`Public Availability of ClinicalTrials.gov .......................................... 60
`3.
`KNUDSEN 2004 [EX. 1032] ....................................................................... 67
`E.
`LUND [EX. 1035] ..................................................................................... 67
`F.
`SEINO [EX. 1038] .................................................................................... 71
`G.
`VICTOZA LABEL [EX. 1039] ...................................................................... 73
`H.
`SHARGEL [EX. 1045] ................................................................................ 75
`I.
`TAMIMI [EX. 1047] .................................................................................. 77
`J.
`FDA EXPOSURE RESPONSE 2003 [EX. 1048] ................................................ 79
`K.
`ICH 1994 [EX. 1049] ............................................................................... 80
`L.
`KNUDSEN 2010B [EX. 1066] ...................................................................... 83
`M.
`ADDITIONAL PRIOR ART AND REFERENCES ................................................... 84
`N.
`IX. UNPATENTABILITY OF THE ’462 PATENT .................................................... 84
`A.
`GROUND 1: WO421 ANTICIPATED CLAIMS 1-3 OF THE ’462 PATENT ................ 84
`1.
`Teachings of WO421 .................................................................... 84
`2.
`WO421 anticipated claim 1 ............................................................ 84
`3.
`WO421 anticipated claim 2 ............................................................ 90
`4.
`WO421 anticipated claim 3 ............................................................ 90
`GROUND 2: LOVSHIN ANTICIPATED CLAIMS 1-3 OF THE ’462 PATENT ............... 91
`1.
`Teachings of Lovshin .................................................................... 91
`2.
`Lovshin anticipated claim 1 ........................................................... 91
`3.
`Lovshin anticipated claim 2 ........................................................... 94
`4.
`Lovshin anticipated claim 3 ........................................................... 95
`GROUND 3: CLAIMS 1-10 OF THE ’462 PATENT WOULD HAVE BEEN
`OBVIOUS OVER WO421 ........................................................................... 95
`1.
`Claim 1 would have been obvious over WO ’421 .............................. 95
`2.
`Claim 2 would have been obvious over WO ’421 ............................ 104
`3.
`Claim 3 would have been obvious over WO ’421 ............................ 104
`-3-
`
`
`
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`TABLE OF CONTENTS
`(continued)
`
`Page
`
`4.
`
`2.
`
`3.
`
`4.
`
`D.
`
`E.
`
`F.
`
`Claims 4-10 would have been obvious over WO ’421 considering
`the ’424 publication .................................................................... 105
`GROUND 4: CLAIMS 1-10 OF THE ’462 PATENT WOULD HAVE BEEN
`OBVIOUS OVER WO537 CONSIDERING LOVSHIN ........................................ 105
`1.
`Claim 1 would have been obvious over WO537 considering
`Lovshin .................................................................................... 105
`Claim 2 would have been obvious over WO537 considering
`Lovshin .................................................................................... 114
`Claim 3 would have been obvious over WO537 considering
`Lovshin .................................................................................... 114
`Claims 4-10 would have been obvious over WO537 considering
`Lovshin .................................................................................... 115
`GROUND 5: CLAIMS 1-10 OF THE ’462 PATENT WOULD HAVE BEEN
`OBVIOUS OVER NCT657 AND NCT773 ..................................................... 116
`1.
`Claim 1 would have been obvious over NCT657 and NCT773 .......... 116
`2.
`Claim 2 would have been obvious over NCT657 and NCT773 .......... 124
`3.
`Claim 3 would have been obvious over NCT657 and NCT773 .......... 124
`4.
`Claims 4-10 would have been obvious over NCT657, NCT773,
`and the ’424 publication .............................................................. 125
`NO SECONDARY CONSIDERATIONS OVERCOME PRIMA FACIE OBVIOUSNESS
`OF THE CLAIMED ALLEGED INVENTIONS .................................................... 126
`1.
`No unexpected results ................................................................. 126
`2.
`No long-felt, unmet need or skepticism .......................................... 126
`CONCLUSION .............................................................................................. 127
`
`-4-
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`
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`X.
`
`
`
`
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`
`
`
`
`
`
`TABLE OF ABBREVIATIONS
`
`Full Name of Cited Reference
`U.S. Patent App. Pub. No. 2011/0166321
`U.S. Patent App. Pub. No. US2007/0010424
`U.S. Patent No. 10,335,462
`U.S. Patent App. Pub. No. 2004/0102486
`U.S. Patent No. 5,512,549
`Bell, Hamster Preproglucagon Contains the Sequence of
`Glucagon and Two Related Peptides, 302 NATURE 716
`(1983)
`Blonde, Comparison of Liraglutide Versus Other Incretin-
`Related Anti-Hyperglycaemic Agents, 14 (suppl. 2)
`DIABETES, OBESITY & METABOLISM 20 (2012)
`Drab, Incretin-Based Therapies for Type 2 Diabetes
`Mellitus: Current Status and Future Prospects, 30
`PHARMACOTHERAPY 609 (2010)
`FDA Guidance for Industry, Exposure-Response
`Relationships - Study Design, Data, Analysis, and
`Regulatory Applications (Apr. 2003)
`Garber, Efficacy of Metformin in Type II Diabetes: Results
`of a Double-Blind, Placebo-Controlled, Dose-Response
`Trial, 102 AM. J. MED. 491 (1997)
`Holst, Truncated Glucagon-like Peptide I, an Insulin-
`Releasing Hormone from the Distal Gut, 211 (2) FEBS
`LETTERS 169 (1987)
`International Conference on Harmonisation; Dose-
`Response Information to Support Drug Registration;
`Guideline; Availability, 59 Fed. Reg. 55972 (Nov. 9, 1994)
`Kirillova, Results and Outcome Reporting in
`ClinicalTrials.gov, What Makes it Happen?, 7(6) PLOS
`ONE 1 (2012)
`
`
`
`
`
`-5-
`
`
`
`Abbreviation
`’321 publication
`’424 publication
`’462 patent
`’486 publication
`’549 patent
`Bell
`
`Blonde
`
`Drab
`
`FDA Exposure Response
`2003
`
`Garber
`
`Holst
`
`ICH 1994
`
`Kirillova
`
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`
`
`
`
`
`
`TABLE OF ABBREVIATIONS
`(continued)
`
`Full Name of Cited Reference
`Knudsen, Glucagon-like Peptide-1: The Basis of a New
`Class of Treatment for Type 2 Diabetes, 47 J. MED.
`CHEMISTRY 4128 (2004)
`Knudsen, Liraglutide: The Therapeutic Promise from
`Animal Models, 64(suppl 167) INT J CLIN PRACT 4 (2010)
`Landersdorfer, Pharmacokinetic/Pharmacodynamic
`Modelling in Diabetes Mellitus, 47(7) CLIN
`PHARMACOKINET 417 (2008)
`Landersdorfer, Mechanism-Based Population
`Pharmacokinetic Modelling in Diabetes: Vildagliptin as a
`Tight Binding Inhibitor and Substrate of Dipeptidyl
`Peptidase IV, 73 Br J Clin Pharmacol 391 (2011)
`Landersdorfer, Mechanism-Based Population Modelling of
`the Effects of Vildagliptin on GLP-1, Glucose and Insulin
`in Patients with Type 2 Diabetes, 73 BR J CLIN
`PHARMACOL 373 (2011)
`Lovshin, Incretin-Based Therapies for Type 2 Diabetes
`Mellitus, 5 NATURE REVIEWS ENDOCRINOLOGY 262 (2009)
`Lund, Emerging GLP-1Receptor Agonists, 16 EXPERT
`OPINION ON EMERGING DRUGS 607 (2011)
`Madsbad, An Overview of Once-Weekly Glucagon-Like
`Peptide-1 Receptor Agonists - Available Efficacy and
`Safety Data and Perspectives for the Future, 13 DIABETES,
`OBESITY & METABOLISM 394 (2011)
`Mojsov, Insulinotropin: Glucagon-like Peptide I (7-37)
`Co-encoded in the Glucagon Gene is a Potent Simulator of
`Insulin Release in the Perfused Rat Pancreas, 79 J. CLIN.
`INVEST. 616 (1987)
`Møller, Mechanism-Based Population Modelling for
`Assessment of L-Cell Function Based on Total GLP-1
`Response Following an Oral Glucose Tolerance Test, 38 J.
`PHARMACOKINET PHARMACODYN 713 (2011)
`
`- 6 -
`
`Abbreviation
`Knudsen 2004
`
`Knudsen 2010b
`
`Landersdorfer 2008
`
`Landersdorfer 2011a
`
`Landersdorfer 2011b
`
`Lovshin
`
`Lund
`
`Madsbad
`
`Mojsov
`
`Moller
`
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`
`
`
`
`
`TABLE OF ABBREVIATIONS
`(continued)
`
`Full Name of Cited Reference
`Monami, Effects of Glucagon-Like Peptide-1 Receptor
`Agonists on Body Weight: A Meta-Analysis, 2012
`EXPERIMENTAL DIABETES RSCH. 1 (2012)
`Murphy, Review of the Safety and Efficacy of Exenatide
`Once Weekly for the Treatment of Type 2 Diabetes
`Mellitus, 46 ANN PHARMACOTHER 812 (2012)
`Clinical Trial No. NCT00696657
`Clinical Trial No. NCT00851773
`Rohatagi, Model-Based Development of a PPARγ Agonist,
`Rivoglitazone, to Aid Dose Selection and Optimize Clinical
`Trial Designs, 48 J. CLIN. PHARM. 1420 (2008)
`Seino, Dose-Dependent Improvement in Glycemia with
`Once-Daily Liraglutide without Hypoglycemia or Weight
`Gain: A Double-Blind, Randomized, Controlled Trial in
`Japanese Patients with Type 2 Diabetes, 81 DIABETES
`RSCH. & CLINICAL PRACTICE 161 (2008)
`Shargel, APPLIED BIOPHARMACEUTICS &
`PHARMACOKINETICS (5th ed. 2005)
`Tamimi, Drug Development: From Concept to Marketing!,
`113 NEPHRON CLIN PRACT C125 (2009)
`Tasneem, The Database for Aggregate Analysis of
`ClinicalTrials.gov (AACT) and Subsequent Regrouping by
`Clinical Specialty, 7(3) PLOS ONE 1(2012)
`Victoza, PHYSICIANS’ DESK REFERENCE (65th ed. 2010)
`International Patent App. Pub. No. WO 2011/058193
`International Patent App. Pub. No. WO 2011/073328
`International Patent App. Pub. No. WO 2011/138421
`International Patent App. Pub. No. WO 91/11457
`International Patent App. Pub. No. WO 2006/097537
`
`Abbreviation
`Monami
`
`Murphy
`
`NCT657
`NCT773
`Rohatagi
`
`Seino
`
`Shargel
`
`Tamimi
`
`Tasneem
`
`Victoza label
`WO193
`WO328
`WO421
`WO457
`WO537
`
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`
`
`
`
`TABLE OF ABBREVIATIONS
`(continued)
`
`Full Name of Cited Reference
`Yun, Pharmacokinetic and Pharmacodynamic Modelling
`of the Effects of Glimepiride on Insulin Secretion and
`Glucose Lowering in Healthy Humans, 31 J. CLIN. PHARM.
`& THER. 469 (2006)
`Zarin, The ClinicalTrials.gov Results Database—Update
`and Key Issues, 364 NEW ENGL. J. MED. 852 (2011)
`
`Abbreviation
`Yun
`
`Zarin
`
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`
`
`1. My name is William J. Jusko, Ph.D. I have been retained by counsel
`
`for Petitioner Mylan Pharmaceuticals Inc. (“Mylan”). I understand that Mylan is
`
`submitting a petition for inter partes review (“IPR”) of U.S. Patent No. 10,335,462
`
`(“’462 patent,” attached as Ex. 1001), which is assigned to Novo Nordisk A/S. It is
`
`my understanding that Mylan is requesting that the United States Patent and
`
`Trademark Office (“USPTO”) cancel all claims of the ’462 patent as unpatentable.
`
`I submit this expert declaration in support of Mylan’s IPR petition for the ’462
`
`patent.
`
`I.
`
`QUALIFICATIONS AND BACKGROUND
`A. EDUCATION AND EXPERIENCE
`2.
`I am a Professor of Pharmaceutical Sciences at the University of
`
`Buffalo School of Pharmacy and Pharmaceutical Sciences. My specialty and
`
`research
`
`focus
`
`broadly
`
`include Pharmacokinetics, Pharmacodynamics,
`
`Pharmacogenomics, and Pharmacometrics.
`
`3. My research interests also include theoretical, basic, and clinical
`
`aspects of
`
`the pharmacokinetics
`
`and pharmacodynamics of various
`
`immunosuppressive agents including corticosteroids, as well as drugs used to treat
`
`diabetes, inflammation, and cancer.
`
`4.
`
`I have characterized the effects of diverse drugs in cells, tissues,
`
`animals,
`
`and
`
`human
`
`subjects
`
`and
`
`have
`
`evolved
`
`advanced
`
`
`
`
`
`-9-
`
`
`
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`
`
`pharmacokinetic/pharmacodynamic (“PK/PD”) models for rapidly acting as well as
`
`
`
`cascade-type processes. I also have developed mechanism-based pharmacokinetic,
`
`pharmacodynamic, and disease progression models and computational methods
`
`describing the action of various drugs and utilized mathematical models of drug
`
`action to determine optimal dosage regimens for diverse drugs.
`
`5.
`
`I have worked as a consultant for the Food and Drug Administration
`
`Clinical Pharmacology Advisory Committee, the NIH Pharmacology Study Section,
`
`the Council for International Exchange of Scholars, and for many pharmaceutical
`
`companies.
`
`6.
`
`From 2001 to 2016, I served as chair of the University of Buffalo
`
`Department of Pharmaceutical Sciences. More than 100 students and fellows have
`
`completed research training under my guidance.
`
`7.
`
`I have published more than 670 research articles and serve on the
`
`editorial boards of numerous academic journals, including formally being the editor-
`
`in-chief for the Journal of Pharmacokinetics and Pharmacodynamics.
`
`8.
`
`I received a Bachelor of Pharmacy in 1965 from State University of
`
`New York at Buffalo. I remained at State University of New York at Buffalo where
`
`I completed my Ph.D. in Pharmaceutical Sciences in 1969.
`
`
`
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`
`
`9.
`
`I began my academic career in 1969 as an Assistant Professor of
`
`
`
`Pharmacology at the Boston University School of Medicine, where I remained for
`
`two years.
`
`10.
`
`I have been a faculty member at the University of Buffalo since 1972.
`
`From 1972 to 1974, I was an Assistant Professor of Pharmaceutics at the University
`
`of Buffalo.
`
`11.
`
`I remained at the University of Buffalo from 1974 to present, where I
`
`transitioned through several roles including as the Director of the Doctor of
`
`Pharmacy Program, Vice-Chairman of the Department of Pharmacy, Professor of
`
`Pharmaceutical Sciences, Chair of Pharmaceutical Sciences, and Director of the
`
`Center of Excellence in Pharmacokinetics and Pharmacodynamics. I am now
`
`currently a SUNY Distinguished Professor in Pharmaceutical Sciences.
`
`12. My expertise has been recognized by my peers. I received the 2020
`
`Distinguished Pharmaceutical Scientist Award from the American Association of
`
`Pharmaceutical Sciences (“AAPS”). The Distinguished Pharmaceutical Scientist
`
`Award is the AAPS’s most esteemed honor and is a lifetime achievement that
`
`recognizes an individual who has made substantial contributions to the research and
`
`advancement of pharmaceutical sciences.
`
`13.
`
`I received the 2019 Lewis B. Sheiner Lecturer Award from the
`
`International Society of Pharmacometrics (“ISoP”); the 2018 Oscar B. Hunter
`
`
`
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`
`
`Career Award in Therapeutics from the American Society for Clinical Pharmacology
`
`
`
`and Therapeutics; a coveted MERIT (Method to Extend Research in Time) Award
`
`from the National Institutes of Health (“NIH”); and several other awards.
`
`14.
`
`I have appreciable experience in studying the pharmaceutical and
`
`pharmacological properties of drugs used to treat diabetes. My curriculum vitae
`
`(“CV”) lists at least 31 such publications with 21 involving the study of antidiabetic
`
`drugs or the diabetes disease conditions in animal models (diabetic rats) and 10
`
`pertaining to the study of antidiabetic drugs in healthy or diabetic humans. Part of
`
`this work was supported by the Pfizer Company when I directed my Department’s
`
`participation in the UB/Pfizer Strategic Alliance in PK/PD with millions of dollars
`
`of support from the company.
`
`15.
`
`I am also an inventor on a patent application assigned to SmithKline
`
`Beecham Corporation in which I assisted in the development of their antidiabetic
`
`drug, Avandia (rosiglitazone) and helped to describe the Exposure/Response
`
`(PK/PD) relationships between plasma drug concentrations, lowering of glucose,
`
`and lowering of glycated hemoglobin (HbA1c) concentrations in blood in type 2
`
`diabetic patients. See Ex. 1078 (’486 publication). This drug was approved by the
`
`FDA as the first-in-class known as “insulin sensitizers” that help the uptake of
`
`glucose by transporters into tissues. I later helped the Daiichi Sankyo Company in
`
`developing rivoglitazone, a drug in the same class with similar effects. See Ex. 1044
`
`
`
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`
`
`(Rohatagi). We generated Exposure/Response relationships for a range of doses in
`
`
`
`these studies.
`
`16.
`
`I have particularly relevant experiences pertaining to glucagon-like
`
`peptide-1 (“GLP-1”)-related mechanisms in diabetes, some of which I discuss in
`
`more detail below. I also have considerable experience in designing studies
`
`(including dosing studies) and assessing pharmacokinetic and pharmacodynamic
`
`data from phase I, II, and III clinical trials. This includes clinical trials for the
`
`antidiabetic drugs rosiglitazone, rivoglitazone, pramlintide, vildagliptin, inhaled
`
`insulin and others.
`
`17.
`
`I am currently a consultant for ReveraGen BioPharma, Inc. advising on
`
`dosing in their clinical trials and performing data analyses for their steroid
`
`vamorolone in treating adolescent males with Duchenne muscular dystrophy.
`
`18. A copy of my CV, Exhibit 1006, provides a more comprehensive
`
`review of my work and describes my qualifications in greater detail, including a list
`
`of all publications that I authored during my career.
`
`B.
`19.
`
`PRIOR TESTIMONY
`In the past four years, I have testified in the following proceedings:
`
`
`
`
`
`Kellington v. Bayer, 5:14-CV-00002 (W.D. VA), 2:14-CV-00036-
`WMA;
`
`Hospira Inc. v. Genentech, Inc., IPR2017-00805 (PTAB);
`
`
`
`
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`
`
`
`
`
`
`
`
`
`
`
`
`KVK-Tech, Inc. v. Shire PLC, IPR2018-00290, IPR2018-00293
`(PTAB);
`
`Novartis AG v. Apotex Inc., Civil Action No. 15-6934 (SRC)(CLW);
`
`Tris Pharma, Inc. v. Teva Pharmaceuticals USA, Inc., 2-20-cv-05212
`(D.N.J.).
`C. BASIS FOR OPINIONS AND MATERIALS CONSIDERED
`20. A list of the materials I considered, in addition to my experience,
`
`education, and training, to provide the opinions contained in this declaration is
`
`attached as Exhibit A.
`
`D. RETENTION AND COMPENSATION
`21.
`I have been retained by counsel for Mylan as a technical expert to
`
`provide certain of my opinions regarding the ’462 patent. I receive $800 per hour
`
`for this work. No part of my compensation is dependent upon my opinions given or
`
`the outcome of this proceeding.
`
`II. LEGAL STANDARDS
`22.
`In preparing and forming my opinions set forth in this declaration, I
`
`have been informed by counsel of the relevant legal principles. I applied my
`
`understanding of those principles in forming my opinions. My understanding of
`
`
`
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`
`
`those principles is summarized below.1 I took these principles into account when
`
`
`
`forming my opinions in this proceeding.
`
`23.
`
`I understand that my opinions regarding unpatentability are presented
`
`from the viewpoint of a person of ordinary skill in the art (“POSA” or “skilled
`
`artisan”) in the field of technology of the patent as of the patent’s priority date. In
`
`this declaration, my opinions are premised on the perspective of a POSA at the time
`
`of the earliest claimed priority date for the ’462 patent, which I have been informed
`
`for this proceeding is July 1, 2012.2 See Ex. 1001 (’462 patent) at 1.
`
`24.
`
`I have been informed that Mylan bears the burden of proving
`
`unpatentability by a preponderance of the evidence. I am informed that this
`
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`1 In performing my analysis and reaching my opinions and conclusions, I have been
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`informed of and have been advised to apply various legal principles relating to
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`unpatentability, which I set forth herein. In setting forth these legal standards, it is
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`not my intention to testify about the law. I only provide my understanding of the
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`law, as explained to me by counsel, as a context for the opinions and conclusions I
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`am providing.
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`2 To the extent Patent Owner asserts that the claims of the ’462 patent are entitled
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`to an earlier priority or invention date, I reserve the right to supplement this
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`declaration.
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`MPI EXHIBIT 1005 PAGE 15
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`DR. REDDY’S LABORATORIES, INC.
`IPR2024-00009
`Ex. 1005, p. 15 of 132
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`“preponderance-of-the-evidence” standard means that the Patent Trial and Appeal
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`Board must find it more likely than not that the claims are unpatentable.
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`25.
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`I understand that for a patent claim to be unpatentable as anticipated, a
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`prior art reference must disclose each element of the claim expressly and/or
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`inherently as arranged in the claim.
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`26. Counsel has informed me that the concept of patent obviousness
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`involves four factual inquiries: (1) the scope and content of the prior art; (2) the
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`differences between the claimed invention and the prior art; (3) the level of ordinary
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`skill in the art; and (4) secondary considerations of non-obviousness.
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`27.
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`It is my understanding from counsel that when there is some recognized
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`reason to solve a problem, and there are a finite number of identified, predictable
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`and known solutions, a person of ordinary skill in the art has good reason to pursue
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`the known options within his or her technical grasp. If such an approach leads to the
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`expected success, it is likely not the product of innovation but of ordinary skill and
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`common sense. It is my understanding that any need or problem known in the field
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`of endeavor at the time of invention or addressed by the patent can provide a reason
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`for combining prior art elements to arrive at the claimed subject matter. I understand
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`that only a reasonable expectation of success is necessary to show obviousness.
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`MPI EXHIBIT 1005 PAGE 16
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`DR. REDDY’S LABORATORIES, INC.
`IPR2024-00009
`Ex. 1005, p. 16 of 132
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`III. PERSON OF ORDINARY SKILL IN THE ART
`28.
`In my opinion, the following definition of a person of ordinary skill in
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`the art (“POSA” or “skilled artisan”) applies to the claims of the ’462 patent.
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`29. A POSA here would have had (1) an M.D., a Pharm. D., or a Ph.D. in
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`pharmacy, chemical engineering, bioengineering, chemistry, or related discipline;
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`(2) at least two years of experience in protein or peptide therapeutic development
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`and/or manufacturing or diabetes treatments; and (3) experience with the
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`development, design, manufacture, formulation, or administration of therapeutic
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`agents, and the literature concerning protein or peptide formulation and design, or
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`diabetes treatments.
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`30. Alternatively, the POSA would be (1) a highly skilled scientist lacking
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`an M.D., Pharm. D., or Ph.D., but would have (2) more than five years of experience
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`in the area of protein or peptide therapeutic development and/or manufacturing or
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`diabetes treatments; and/or (3) experience with the development, design,
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`manufacture, formulation, or administration of therapeutic agents, and the literature
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`concerning protein or peptide formulation and design, or diabetes treatments.
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`31. A POSA would have understood the prior art references referred to
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`herein and would have the capability to draw inferences. It is understood that, to the
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`extent necessary, a POSA may collaborate with one or more other POSAs for one or
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`more aspects with which the other POSA may have expertise, experience, and/or
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`MPI EXHIBIT 1005 PAGE 17
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`DR. REDDY’S LABORATORIES, INC.
`IPR2024-00009
`Ex. 1005, p. 17 of 132
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`knowledge. Additionally, a POSA could have had a lower level of formal education
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`than what I describe here if the person has a higher degree of experience.
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`32. As shown by my qualifications provided in my CV and as explained in
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`this declaration, I met the qualifications of a POSA for purposes of the ’462 patent.
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`33.
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`I understand that Mylan’s formulation expert Dr. Paul Dalby is
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`submitting a declaration with his opinions about why claims 4-10 of the ’462 patent,
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`directed to formulation-related elements, are obvious over the prior art. I defer to
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`Dr. Dalby’s opinion on the formulation-related elements of claims 4-10 of the ’462
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`patent.
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`IV. BRIEF SUMMARY OF OPINIONS
`34.
`In my opinion, International Patent Application Publication No. WO
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`2011/138421 (“WO421”) anticipates claims 1-3 of the ’462 patent.
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`35.
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`In my opinion, a review article titled “Incretin-Based Therapies for
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`Type 2 Diabetes Mellitus” (“Lovshin”) authored by Julie A. Lovshin and Daniel J.
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`Drucker, which was published in May 2009, anticipates claims 1-3 of the ’462 patent.
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`36.
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`In my opinion, claims 1-10 of the ’462 patent would have been obvious
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`over WO421 considering U.S. Patent Application Publication No. 2007/0010424 A1
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`(“’424 Publication”). It is my understanding that Dr. Dalby is offering an opinion
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`that claims 4-10 would have been obvious over WO421 considering the ’424
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`Publication, and I defer to his opinion for claims 4-10.
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`MPI EXHIBIT 1005 PAGE 18
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`DR. REDDY’S LABORATORIES, INC.
`IPR2024-00009
`Ex. 1005, p. 18 of 132
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`37.
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`In my opinion, claims 1-10 of the ’462 patent would have been obvious
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`over International Patent Application Publication No. WO 2006/097537 A2
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`(“WO537”) considering Lovshin. It is my understanding that Dr. Dalby is offering
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`an opinion that claims 4-10 would have been obvious over WO537 considering
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`Lovshin, and I defer to his opinion for claims 4-10.
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`38.
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`In my opinion, claims 1-10 of the ’462 patent would have been obvious
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`over Clinical Trial No. NCT00696657 (“NCT657”), Clinical Trial No.
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`NCT00851773 (“NCT773”), and the ’424 Publication. It is my understanding that
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`Dr. Dalby is offering an opinion that claims 4-10 would have been obvious over
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`NCT657, NCT773, and the ’424 Publication, and I defer to his opinion for claims 4-
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`10.
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`39. Finally, there are no apparent secondary considerations supporting
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`nonobviousness of the claims. I reserve the right to address any secondary
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`considerations put forth by Patent Owner in any later response to this declaration or
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`the petition it accompanies.
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`V. THE ’462 PATENT [EX. 1001]
`A. THE SPECIFICATION AND CLAIMS OF THE ’462 PATENT
`40.
`I have read the ’462 patent, titled “Use of Long-Acting GLP-1
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`Peptides,” and reviewed the relevant portions of the prosecution history of the ’462
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`patent (Ex. 1002). The ’462 patent issued from U.S. Patent Application No.
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`MPI EXHIBIT 1005 PAGE 19
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`DR. REDDY’S LABORATORIES, INC.
`IPR2024-00009
`Ex. 1005, p. 19 of 132
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`15/656,042 (“’042 Application”), filed July 21, 2017, which is a continuation of U.S.
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`
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`Application No. 14/409,493, filed as PCT/EP2013/063004, filed June 21, 2013, and
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`claims priority to Provisional Application No. 61/708,162, filed October 1, 2012,
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`and Provisional Application No. 61/694,837, filed August 30, 2012, and European
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`patent 12174535, filed July 1, 2012, and European patent 12186781, filed October
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`1, 2012. Ex. 1001 (’462 patent) at 1. The ’462 patent lists Christine Bjoern Jensen
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`as the sole inventor and Novo Nordisk A/S as the Assignee. Id.
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`41. The ’462 patent has one independent claim and nine dependent claims.
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`42.
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`Independent claim 1 recites “[a]method for treating type 2 diabetes,
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`comprising administering semaglutide once weekly in an amount of 1.0 mg to a
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`subject in need thereof.”
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`43. Claim 2 recites, “[t]he method according to claim 1, wherein the
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`semaglutide is administered by parenteral administration.”
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`44. Claim 3 recites, “[t]he method according to claim 2, wherein the
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`solution is administered by subcutaneous injection.”
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`45. Claim 4 recites, “[t]he method according to claim 1, wherein the
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`semaglutide is administered in the form of an isotonic aqueous solution comprising
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`phosphate buffer at a pH in the range of 7.0-9.0.”
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`46. Claim 5 recites, “[t]he method according to claim 4, wherein the
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`solution further comprises propylene glycol and phenol.”
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`MPI EXHIBIT 1005 PAGE 20
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`DR. REDDY’S LABORATORIES, INC.
`IPR2024-00009
`Ex. 1005, p. 20 of 132
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`47. Claim 6 recites, “[t]he method according to claim 4, wherein the pH is
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`7.4.”
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`48. Claim 7 recites, “[t]he method according to claim 6, wherein the
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`solution further comprises propylene glycol and phenol.”
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`49. Claim 8 recites, “[t]he method according to claim 4, wherein the
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`phosphate buffer is a sodium dihydrogen phosphate buffer.”
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`50. Claim 9 recites, “[t]he method according to claim 1, wherein the
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`semaglutide is administered by subcutaneous injection in the form of an isotonic
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`aqueous solution comprising at a sodium dihydrogen phosphate buffer at a pH in the
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`range of 7.0-9.0, and wherein the solution further comprises propylene glycol and
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`phenol.”
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`51. Claim 10 recites, “[t]he method according to claim 9, wherein the pH
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`is 7.4.”
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`B.
`THE PROSECUTION HISTORY OF THE ’462 PATENT
`52. The ’042 Application that issued as the ’462 patent was filed on July
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`21, 2017 and includ